Publications by authors named "Hongmei Zhang"

682 Publications

Corrigendum to 'Draft genome sequence of a metallo-β lactamase (blaAIM-1)-producing Klebsiella pneumoniae ST1916 isolated from a patient with chronic diarrhoea' [Journal of Global Antimicrobial Resistance 16 (2019) 165-167].

J Glob Antimicrob Resist 2021 Sep 18;26:345. Epub 2021 Jul 18.

Laboratory of Microbiology and Immunology, Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, No. 40 North Daxue Road, Zhengzhou, He'nan 450052, China. Electronic address:

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http://dx.doi.org/10.1016/j.jgar.2021.06.010DOI Listing
September 2021

Transcriptomic analysis of salt tolerance-associated genes and diversity analysis using indel markers in yardlong bean (Vigna unguiculata ssp. sesquipedialis).

BMC Genom Data 2021 Sep 16;22(1):34. Epub 2021 Sep 16.

Soybean Research Institute of Nanjing Agricultural University/National Center for Soybean Improvement/National Key Laboratory for Crop Genetics and Germplasm Enhancement, Nanjing, 210095, Jiangsu, China.

Background: High salinity is a devastating abiotic stresses for crops. To understand the molecular basis of salinity stress in yardlong bean (Vigna unguiculata ssp. sesquipedalis), and to develop robust markers for improving this trait in germplasm, whole transcriptome RNA sequencing (RNA-seq) was conducted to compare the salt-tolerant variety Suzi 41 and salt-sensitive variety Sujiang 1419 under normal and salt stress conditions.

Results: Compared with controls, 417 differentially expressed genes (DEGs) were identified under exposure to high salinity, including 42 up- and 11 down-regulated DEGs in salt-tolerant Suzi 41 and 186 up- and 197 down-regulated genes in salt-sensitive Sujiang 1419, validated by qRT-PCR. DEGs were enriched in "Glycolysis/Gluconeogenesis" (ko00010), "Cutin, suberine and wax biosynthesis" (ko00073), and "phenylpropanoid biosynthesis" (ko00940) in Sujiang 1419, although "cysteine/methionine metabolism" (ko00270) was the only pathway significantly enriched in salt-tolerant Suzi 41. Notably, AP2/ERF, LR48, WRKY, and bHLH family transcription factors (TFs) were up-regulated under high salt conditions. Genetic diversity analysis of 84 yardlong bean accessions using 26 InDel markers developed here could distinguish salt-tolerant and salt-sensitive varieties.

Conclusions: These findings show a limited set of DEGs, primarily TFs, respond to salinity stress in V. unguiculata, and that these InDels associated with salt-inducible loci are reliable for diversity analysis.
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http://dx.doi.org/10.1186/s12863-021-00989-wDOI Listing
September 2021

Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation.

Nat Genet 2021 Sep 6;53(9):1311-1321. Epub 2021 Sep 6.

Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.

Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.
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http://dx.doi.org/10.1038/s41588-021-00923-xDOI Listing
September 2021

Dorsal root ganglion toll-like receptor 4 signaling contributes to oxaliplatin-induced peripheral neuropathy.

Pain 2021 Sep 2. Epub 2021 Sep 2.

Department of Anesthesiology and Pain Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan Department of Urology, Chang Gung Memorial Hospital, Taoyuan, Taiwan Department of Anesthesiology and Perioperative Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States.

Abstract: Activation of toll-like receptor 4 (TLR4) in the dorsal root ganglion (DRG) and spinal cord contributes to the generation of paclitaxel-related chemotherapy-induced peripheral neuropathy (CIPN). Generalizability of TLR4 signaling in oxaliplatin-induced CIPN was tested here. Mechanical hypersensitivity developed in male SD rats by day 1 after oxaliplatin treatment, reached maximum intensity by day 14, and persisted through day 35. Western blot revealed an increase in TLR4 expression in the DRG of oxaliplatin at days 1 and 7 after oxaliplatin treatment. Cotreatment of rats with the TLR4 antagonist lipopolysaccharide derived from Rhodobacter sphaeroides ultrapure or with the nonspecific immunosuppressive minocycline with oxaliplatin resulted in significantly attenuated hyperalgesia on day 7 and 14 compared with rats that received oxaliplatin plus saline vehicle. Immunostaining of DRGs revealed an increase in the number of neurons expressing TLR4, its canonical downstream signal molecules myeloid differentiation primary response gene 88 (MyD88) and TIR-domain-containing adapter-inducing interferon-β, at both day 7 and day 14 after oxaliplatin treatment. These increases were blocked by cotreatment with either lipopolysaccharide derived from Rhodobacter sphaeroides or minocycline. Double staining showed the localization of TLR4, MyD88, and TIR-domain-containing adapter-inducing interferon-β in subsets of DRG neurons. Finally, there was no significant difference in oxaliplatin-induced mechanical hypersensitivity between male and female rats when observed for 2 weeks. Furthermore, upregulation of TLR4 was detected in both sexes when tested 14 days after treatment with oxaliplatin. These findings suggest that the activation of TLR4 signaling in DRG neurons is a common mechanism in CIPN induced by multiple cancer chemotherapy agents.
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http://dx.doi.org/10.1097/j.pain.0000000000002454DOI Listing
September 2021

Multiple-level copy number variations in cell-free DNA for prognostic prediction of HCC with radical treatments.

Cancer Sci 2021 Sep 6. Epub 2021 Sep 6.

Department of Physiology and Pathophysiology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China.

Copy number variations (CNVs) in cell-free DNA (cfDNA) are emerging as noninvasive biomarkers for various cancers. However, multiple-level analysis of cfDNA CNVs for hepatocellular carcinoma (HCC) patients with radical treatments remains uninvestigated. Here, CNVs at genome-wide, chromosomal-arm, and bin levels were analyzed in cfDNA from 117 HCC patients receiving radical treatments. Then, the relationship between cfDNA CNVs and clinical outcomes was explored. Our results showed that a concordant profile of CNVs was observed between cfDNA and tumor tissue DNA. Three genome-wide CNV indicators including tumor fraction (TFx), prediction score (P-score), and stability score (S-score) were calculated and demonstrated to exhibit significant correlation with poorer overall survival (OS) and recurrence-free survival (RFS). Furthermore, the high-frequency cfDNA CNVs at chromosomal-arm level including the loss of 4q, 17p, and 19p and the gain of 8q and 1q clearly predicted HCC prognosis. Finally, a bin-level risk score was constructed to improve the ability of CNVs in predicting prognosis. Altogether, our study indicates that the multiple-level cfDNA CNVs are significantly associated with OS and RFS in HCC patients with radical treatments, suggesting that cfDNA CNVs detected by low-coverage whole-genome sequencing (WGS) may be used as potential prognostic biomarkers of HCC patients.
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http://dx.doi.org/10.1111/cas.15128DOI Listing
September 2021

Clinicopathological significance and prognostic value of P27 expression in gastric cancer patients: a meta-analysis.

Anticancer Drugs 2021 Sep 2. Epub 2021 Sep 2.

Department of Laboratory Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine Pharmacy Department, People's Hospital of Lixia District of Jinan, Jinan, Shandong, China.

Loss of P27 expression correlates with clinical progression in a variety of human cancers. However, the correlation between P27 expression and gastric cancer remains controversial. In this meta-analysis, we performed an electronic search based on six databases to select a sufficient number of studies. Pooled hazard ratio (HR) was used as estimates to investigate the association between P27 expression and prognosis of patients with gastric cancer. We identified 19 studies with 2387 gastric cancer patients, ranging between 50 and 316 samples per study. Q and I2 tests demonstrated that the homogeneity among 19 studies (I2 = 47%, P = 0.0004), thus we applied a fixed-effects model to calculate the pooled HR of P27expression and overall survival (OS) of gastric cancer patients was 0.68, and 95% confidence interval (CI) was 0.60-0.78. Next, we conducted a subgroup meta-analysis and found that patients with low P27 expression in Asians (HR = 0.69, 95% CI: 0.58-0.82) and non-Asians (HR = 0.57, 95% CI: 0.41-0.79) had poor prognosis. In addition, we found the publication bias results of OS in the final included 19 studies showed that this funnel plot presented incomplete symmetry, and then removed three literatures with larger HRs bias, and found that the remaining 16 literatures were homogeneity (I2 = 0%, P = 0.47), the pooled HR was 0.52 with 95% CI of 0.43-0.62, and the publication bias disappeared. These results suggested a strong association between P27 underexpression and poorer prognosis of gastric cancer in patients. P27 may be a tumor suppressor for predicting survival outcome of gastric cancer patients.
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http://dx.doi.org/10.1097/CAD.0000000000001240DOI Listing
September 2021

Role of aneuploid circulating tumor cells and CD31 circulating tumor endothelial cells in predicting and monitoring anti-angiogenic therapy efficacy in advanced NSCLC.

Mol Oncol 2021 Aug 28. Epub 2021 Aug 28.

Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.

Prognosticating the efficacy of anti-angiogenic therapy through longitudinal monitoring and early detection of treatment resistance in cancer patients remain highly challenging. In this study, co-detection and comprehensive phenotypic and karyotypic molecular characterization of aneuploid circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) were conducted on non-small cell lung cancer (NSCLC) patients receiving bevacizumab plus chemotherapy. Prognostic values of the cell-based significant univariate risk factors identified by Cox regression analyses were progressively investigated. Subjects showing an increase in total post-therapeutic platelet endothelial cell adhesion molecule-1 (CD31) CTCs and CD31 CTECs exhibited a significantly reduced median progression-free survival (mPFS) and overall survival. Further stratification analyses indicated that pretherapeutic patients bearing vimentin (Vim) CTECs (mesenchymal M-type) at baseline revealed a significantly shortened mPFS compared with patients with Vim CTECs. Post-therapeutic patients harboring epithelial cell adhesion molecule (EpCAM) CTCs and CTECs (epithelial E-type), regardless of Vim expression or not, showed a significantly reduced mPFS. Post-therapeutic patients possessing de novo EpCAM /Vim (hybrid E/M-type) CTECs displayed the shortest mPFS. Patients harboring either pre- or post-therapeutic EpCAM /Vim null CTECs (N-type) exhibited a better response to therapy compared to patients harboring EpCAM and/or Vim CTECs. The presented results support the notion that baseline Vim CTECs and post-therapeutic EpCAM CTCs and CTECs are predictive biomarkers for longitudinal monitoring of response to anti-angiogenesis combination regimens in NSCLC patients.
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http://dx.doi.org/10.1002/1878-0261.13092DOI Listing
August 2021

Methylation of Host Genes Associated with Coronavirus Infection from Birth to 26 Years.

Genes (Basel) 2021 07 31;12(8). Epub 2021 Jul 31.

Division of Epidemiology, Biostatistics, and Environmental Health Sciences, School of Public Health, University of Memphis, Memphis, TN 38111, USA.

DNA methylation (DNAm) patterns over time at 1146 CpGs on coronavirus-related genes were assessed to understand whether the varying differences in susceptibility, symptoms, and the outcomes of the SARS-CoV-2 infection in children and young adults could be explained through epigenetic alterations in a host cell's transcriptional apparatus to coronaviruses. DNAm data from the Isle of Wight birth cohort (IOWBC) at birth, 10, 18, and 26 years of age were included. Linear mixed models with repeated measurements stratified by sex were used to examine temporal patterns, and cluster analysis was performed to identify CpGs following similar patterns. CpGs on autosomes and sex chromosomes were analyzed separately. The association of identified CpGs and expression of their genes were evaluated. Pathway enrichment analyses of the genes was conducted at FDR = 0.05. DNAm at 635 of the 1146 CpGs on autosomes showed statistically significant time effects (FDR = 0.05). The 635 CpGs were classified into five clusters with each representing a unique temporal pattern of DNAm. Of the 29 CpGs on sex chromosomes, DNAm at seven CpGs in males and eight CpGs in females showed time effects (FDR = 0.05). Sex-specific and non-specific associations of DNAm with gene expression were found at 24 and 93 CpGs, respectively. Genes which mapped the 643 CpGs represent 460 biological processes. We suggest that the observed variability in DNAm with advancing age may partially explain differing susceptibility, disease severity, and mortality of coronavirus infections among different age groups.
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http://dx.doi.org/10.3390/genes12081198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392033PMC
July 2021

Confining isolated chromophores for highly efficient blue phosphorescence.

Nat Mater 2021 Aug 23. Epub 2021 Aug 23.

Key Laboratory of Flexible Electronics and Institute of Advanced Materials, Nanjing Tech University, Nanjing, China.

High-efficiency blue phosphorescence emission is essential for organic optoelectronic applications. However, synthesizing heavy-atom-free organic systems having high triplet energy levels and suppressed non-radiative transitions-key requirements for efficient blue phosphorescence-has proved difficult. Here we demonstrate a simple chemical strategy for achieving high-performance blue phosphors, based on confining isolated chromophores in ionic crystals. Formation of high-density ionic bonds between the cations of ionic crystals and the carboxylic acid groups of the chromophores leads to a segregated molecular arrangement with negligible inter-chromophore interactions. We show that tunable phosphorescence from blue to deep blue with a maximum phosphorescence efficiency of 96.5% can be achieved by varying the charged chromophores and their counterions. Moreover, these phosphorescent materials enable rapid, high-throughput data encryption, fingerprint identification and afterglow display. This work will facilitate the design of high-efficiency blue organic phosphors and extend the domain of organic phosphorescence to new applications.
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http://dx.doi.org/10.1038/s41563-021-01073-5DOI Listing
August 2021

Purinergic Receptor P2Y Is a Negative Regulator of NK Cell Maturation and Function.

J Immunol 2021 09 23;207(6):1555-1565. Epub 2021 Aug 23.

Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China

NK cells are critical innate immune cells that target the tumor cells and cancer-initiating cells and clear viruses by producing cytokines and cytotoxic granules. However, the role of the purinergic receptor P2Y in the NK cells remains largely unknown. In this study, we discovered that the expression of P2Y was decreased upon the activation of the NK cells. Moreover, in the P2Y-deficient mice, we found that the deficiency of P2Y promoted the development of the NK precursor cells into immature NK and mature NK cells. We also found that the P2Y deficiency increased, but the P2Y receptor agonist UDP or UDP analog 5-OMe-UDP decreased the production of IFN-γ in the activated NK cells. Furthermore, we demonstrated that the P2Y-deficient NK cells exhibited stronger cytotoxicity in vitro and antimetastatic effects in vivo. Mechanistically, P2Y deletion promoted the expression of T-bet (encoded by Tbx21), with or without the stimulation of IL-15. In the absence of P2Y, the levels of phospho-serine/threonine kinase and pS6 in the NK cells were significantly increased upon the stimulation of IL-15. Collectively, we demonstrated that the P2Y receptor acted as a negative regulator of the NK cell function and inhibited the maturation and antitumor activities of the NK cells. Therefore, inhibition of the P2Y receptor increases the antitumor activities of the NK cells, which may aid in the design of innovative strategies to improve NK cell-based cancer therapy.
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http://dx.doi.org/10.4049/jimmunol.2000750DOI Listing
September 2021

Precision Therapy for a Chinese Family With Maturity-Onset Diabetes of the Young.

Front Endocrinol (Lausanne) 2021 5;12:700342. Epub 2021 Aug 5.

Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: To determine the pathogenic gene and explore the clinical characteristics of maturity-onset diabetes of the young type 2 (MODY2) pedigree caused by a mutation in the glucokinase () gene.

Methods: Using whole-exome sequencing (WES), the pathogenic gene was detected in the proband-a 20-year-old young man who was accidentally found with hyperglycemia, no ketosis tendency, and a family history of diabetes. The family members of the proband were examined. In addition, relevant clinical data were obtained and genomic DNA from peripheral blood was obtained. Pathologic variants of the candidate were verified by Sanger sequencing technology, and cosegregation tests were conducted among other family members and non-related healthy controls. After adjusting the treatment plan based on the results of genetic testing, changes in biochemical parameters, such as blood glucose levels and HAblc levels were determined.

Results: In the gene (NM_000162) in exon 9, a heterozygous missense mutation c.1160C > T (p.Ala387Val) was found in the proband, his father, uncle, and grandmother. Thus mutation, which was found to co-segregate with diabetes, was the first discovery of such a mutation in the Asian population. After stopping hypoglycemic drug treatment, good glycemic control was achieved with diet and exercise therapy.

Conclusion: gene mutation c.1160C > T (p.Ala387Val) is the pathogenic gene in the pedigree. Formulating an optimized and personalized treatment strategy can reduce unnecessary excessive medical treatment and adverse drug reactions, and maintain a good HbA1c compliance rate.
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http://dx.doi.org/10.3389/fendo.2021.700342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374143PMC
August 2021

A preliminary study of synthetic magnetic resonance imaging in rectal cancer: imaging quality and preoperative assessment.

Insights Imaging 2021 Aug 21;12(1):120. Epub 2021 Aug 21.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.

Purpose: To compare the imaging quality, T stage and extramural venous invasion (EMVI) evaluation between the conventional and synthetic T2-weighted imaging (T2WI), and to investigate the role of quantitative values obtained from synthetic magnetic resonance imaging (MRI) for assessing nodal staging in rectal cancer (RC).

Methods: Ninety-four patients with pathologically proven RC who underwent rectal MRI examinations including synthetic MRI were retrospectively recruited. The image quality of conventional and synthetic T2WI was compared regarding signal-to-noise ratio (SNR), contrast-to-noise (CNR), sharpness of the lesion edge, lesion conspicuity, absence of motion artifacts, and overall image quality. The accuracy of T stage and EMVI evaluation on conventional and synthetic T2WI were compared using the Mc-Nemar test. The quantitative T1, T2, and PD values were used to predict the nodal staging of MRI-evaluated node-negative RC.

Results: There were no statistically significant differences between conventional and synthetic T2WI in SNR, CNR, overall image quality, lesion conspicuity, and absence of motion artifacts (p = 0.058-0.978). There were no significant differences in the diagnostic accuracy of T stage and EMVI between conventional and synthetic T2WI from two observers (p = 0.375 and 0.625 for T stage; p = 0.625 and 0.219 for EMVI). The T2 value showed good diagnostic performance for predicting the nodal staging of RC with the area under the receiver operating characteristic, sensitivity, specificity, and accuracy of 0.854, 90.0%, 71.4%, and 80.3%, respectively.

Conclusions: Synthetic MRI may facilitate preoperative staging and EMVI evaluation of RC by providing synthetic T2WI and quantitative maps in one acquisition.
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http://dx.doi.org/10.1186/s13244-021-01063-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380206PMC
August 2021

Distribution of diabetic retinopathy in diabetes mellitus patients and its association rules with other eye diseases.

Sci Rep 2021 Aug 20;11(1):16993. Epub 2021 Aug 20.

Henan Eye Institute, Henan Eye Hospital, and Henan Key Laboratory of Ophthalmology and Visual Science, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou City, 450000, China.

The study aims to explore the distribution characteristics and influencing factors of diabetic retinopathy (DR) in diabetes mellitus (DM) patients and association rules of eye diseases in these patients. Data were obtained from 1284 DM patients at Henan Provincial People's Hospital. Association rules were employed to calculate the probability of the common occurrence of eye-related diseases in DM patients. A web visualization network diagram was used to display the association rules of the eye-related diseases in DM patients. DR prevalence in people aged < 40 years (≥ 58.5%) was higher than that in those aged 50-60 years (≤ 43.7%). Patients with DM in rural areas were more likely to have DR than those in urban areas (56.2% vs. 35.6%, P < 0.001). DR prevalence in Pingdingshan City (68.4%) was significantly higher than in other cities. The prevalence of DR in patients who had DM for ≥ 5 years was higher than in other groups (P < 0.001). About 33.07% of DM patients had both diabetic maculopathy and DR, and 36.02% had both diabetic maculopathy and cataracts. The number of strong rules in patients ≥ 60 years old was more than those in people under 60 in age, and those in rural areas had more strong rules than those in urban areas. DM patients with one or more eye diseases are at higher risks of other eye diseases than general DM patients. These association rules are affected by factors such as age, region, disease duration, and DR severity.
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http://dx.doi.org/10.1038/s41598-021-96438-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379227PMC
August 2021

PKCι regulates the expression of PDL1 through multiple pathways to modulate immune suppression of pancreatic cancer cells.

Cell Signal 2021 Oct 8;86:110115. Epub 2021 Aug 8.

Department of Immunology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, 3-17 Renmin South Road, Chengdu, Sichuan 610041, PR China. Electronic address:

To investigate the impact of oncogenic protein kinase C isoform ι (PKCι) on the microenvironment and the immunogenic properties of pancreatic tumors, we prohibit PKCι activity in various pancreatic ductal adenocarcinoma (PDAC) cell lines and co-culture them with human natural killer NK92 cells. The results demonstrate that PKCι suppression enhances the susceptibility of PDAC to NK cytotoxicity and promotes the degranulation and cytolytic activity of co-cultured NK92 cells. Mechanistic studies pinpoint that downstream of KRAS, both YAP1 and STAT3 are recruited by oncogenic PKCι to elevate the expression of PDL1, contributing to constitute an immune suppressive microenvironment in PDAC. Co-culture with NK92 further induces PDL1 upregulation via STAT3 to stimulate immune escape of PDAC cells. Subsequently, inhibition of PKCι in PDAC alleviates the immune suppression and enhances the cytotoxicity of NK92 towards PDAC through restraining PDL1 overexpression. Combined with PD1/PDL1 blocker, PKCι inhibitor remarkably elevates the cytotoxicity of NK92 against PDAC cells in vitro, establishing PKCι inhibitor as a promising candidate for boosting the immunotherapy of PDAC.
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http://dx.doi.org/10.1016/j.cellsig.2021.110115DOI Listing
October 2021

Corrigendum to "RECIST 1.1, Choi and mChoi criteria in the evaluation of tumor response in patients with metastatic colorectal cancer treated with Regorafenib and anti-PD-1 antibody" [Eur. J. Radiol. 141 (2021) 109823].

Eur J Radiol 2021 Sep 6;142:109897. Epub 2021 Aug 6.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.

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http://dx.doi.org/10.1016/j.ejrad.2021.109897DOI Listing
September 2021

Serum creatinine levels and risk of nonalcohol fatty liver disease in a middle-aged and older Chinese population: A cross-sectional analysis.

Diabetes Metab Res Rev 2021 Aug 3:e3489. Epub 2021 Aug 3.

Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Non-alcoholic fatty liver disease (NAFLD) is now regarded as the hepatic manifestation of metabolic syndrome (MetS). Recent research has suggested that serum creatinine (SCr) may be an indicator of MetS and its related diseases. We aimed to investigate the association between SCr and NAFLD in Chinese adults.

Methods: A cross-sectional sample of 8862 subjects aged 40 years or older (40-73 years) from China were analysed in this study. The anthropometric measurements, laboratory tests, and hepatic ultrasonography were conducted. NAFLD presence was defined by hepatic ultrasound in the absence of other liver diseases.

Results: NAFLD subjects had higher SCr than those without NAFLD (66.8 μmol/L vs. 65.6 μmol/L, p < 0.001). Moreover, SCr levels were correlated with alanine aminotransferase (β = 0.099, p < 0.001), aspartate aminotransferase (β = 0.135, p < 0.001), γ-glutamyltransferase (β = 0.039, p < 0.001), and insulin resistance (β = 0.027, p = 0.014) after adjusted for potential covariates. In the multivariable-adjusted logistic regression analyses, compared to the first SCr quintile, the odds ratio for NAFLD was 1.35 (95% confidence interval 1.14-1.60, p < 0.001) for the fifth quintile after adjusting multiple measured confounders.

Conclusion: SCr concentration is independently associated with NAFLD in a middle aged and older Chinese population. Elevated SCr levels, even within normal ranges, were associated with higher risk of NAFLD.
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http://dx.doi.org/10.1002/dmrr.3489DOI Listing
August 2021

Simultaneous LC-MS/MS bioanalysis of alkaloids, terpenoids, and flavonoids in rat plasma through salting-out-assisted liquid-liquid extraction after oral administration of extract from Tetradium ruticarpum and Glycyrrhiza uralensis: a sample preparation strategy to broaden analyte coverage of herbal medicines.

Anal Bioanal Chem 2021 Sep 31;413(23):5871-5884. Epub 2021 Jul 31.

Institute of Chinese Materia Medica, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, China.

Herbal medicines have historically been practiced in combinatorial way, which achieves therapeutic efficacy by integrative effects of multi-components. Thus, the accurate and precise measurement of multi bioactive components in matrices is inalienable to understanding the metabolism and disposition of herbal medicines. In this study, aiming to provide a strategy that improves analyte coverage, evaluation of six protocols employing sample pretreatment methods- protein precipitation (PPT), liquid-liquid extraction (LLE), sugaring-out-assisted liquid-liquid extraction (SULLE), and salting-out-assisted liquid-liquid extraction (SALLE)- was performed by LC-MS/MS using rat plasma and a mixture of alkaloid (evodiamine, rutaecarpine, dehydroevodiamine), terpenoid (limonin, rutaevin, obacunone), and flavonoid (liquiritin, isoliquiritin, liquiritigenin) standards isolated from Tetradium ruticarpum and Glycyrrhiza uralensis. These protocols were as follows: (1) PPT with methanol, (2) PPT with acetonitrile, (3) LLE with methyl tertiary-butyl ether-dichloromethane, (4) LLE with ethyl acetate-n-butanol, (5) SALLE with ammonium acetate, (6) SULLE with glucose. The results suggested that SALLE produced broader analyte coverage with satisfactory reproducibility, acceptable recovery, and low matrix interference. Then, sample preparation procedure of SALLE, chromatographic conditions, and mass spectrometric parameters were optimized, followed by method validation, showing that good sensitivity (LLOQ ≤ 1 ng mL), linearity (r ≥ 0.9933), precision (RSD ≤ 14.45%), accuracy (89.54~110.87%), and stability could be achieved. Next, the developed method was applied successfully to determine the pharmacokinetic behavior of the nine compounds in rat plasma after intragastric administration with an extract from Tetradium ruticarpum and Glycyrrhiza uralensis (Wuzhuyu-Gancao pair). Based on an extensive review and experiments, a sample preparation procedure that matches with LC-MS/MS technique and can get wider analyte coverage was outlined. The developed SALLE method is rapid, reliable, and suitable for bioanalysis of analytes with diverse polarity, which was expected to be a promising strategy for the pharmacokinetic studies of herbal medicines. Graphical abstract.
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http://dx.doi.org/10.1007/s00216-021-03568-1DOI Listing
September 2021

Histogram models based on intravoxel incoherent motion diffusion-weighted imaging to predict nodal staging of rectal cancer.

Eur J Radiol 2021 Sep 20;142:109869. Epub 2021 Jul 20.

Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. No.17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. Electronic address:

Purpose: To develop a model based on histogram parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for predicting the nodal staging of rectal cancer (RC).

Material And Methods: A total of 95 RC patients who underwent direct surgical resection were enrolled in this prospective study. The nodal staging on conventional magnetic resonance imaging (MRI) was evaluated according to the short axis diameter and morphological characteristics. Histogram parameters were extracted from apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) maps. Multivariate binary logistic regression analysis was conducted to establish models for predicting nodal staging among all patients and those underestimated on conventional MRI.

Results: The combined model based on multiple maps demonstrated superior diagnostic performance to single map models, with an area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy of 0.959, 94.3%, 88.3%, and 90.5%, respectively. The AUC of the combined model was significantly higher than that of the conventional nodal staging (P < 0.001). Additionally, 85.0% of the underestimated patients had suspicious lymph nodes with 5-8 mm short-axis diameter. The histogram model for these subgroups of patients showed good diagnostic efficacy with an AUC, sensitivity, specificity, and accuracy of 0.890, 100%, 75%, and 80.5%.

Conclusion: The histogram model based on IVIM-DWI could improve the diagnostic performance of nodal staging of RC. In addition, histogram parameters of IVIM-DWI may help to reduce the uncertainty of nodal staging in underestimated patients on conventional MRI.
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http://dx.doi.org/10.1016/j.ejrad.2021.109869DOI Listing
September 2021

BMI trajectory in childhood is associated with asthma incidence at young adulthood mediated by DNA methylation.

Allergy Asthma Clin Immunol 2021 Jul 23;17(1):77. Epub 2021 Jul 23.

Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.

Purpose: Body mass index (BMI) is associated with asthma but associations of BMI temporal patterns with asthma incidence are unclear. Previous studies suggest that DNA methylation (DNAm) is associated with asthma status and variation in DNAm is a consequence of BMI changes. This study assessed the direct and indirect (via DNAm) effects of BMI trajectories in childhood on asthma incidence at young adulthood.

Methods: Data from the Isle of Wight (IoW) birth cohort were included in the analyses. Group-based trajectory modelling was applied to infer latent BMI trajectories from ages 1 to 10 years. An R package, ttscreening, was applied to identify differentially methylated CpGs at age 10 years associated with BMI trajectories, stratified for sex. Logistic regressions were used to further exclude CpGs with DNAm at age 10 years not associated with asthma incidence at 18 years. CpGs discovered via path analyses that mediated the association of BMI trajectories with asthma incidence in the IoW cohort were further tested in an independent cohort, the Avon Longitudinal Study of Children and Parents (ALSPAC).

Results: Two BMI trajectories (high vs. normal) were identified. Of the 442,474 CpG sites, DNAm at 159 CpGs in males and 212 in females were potentially associated with BMI trajectories. Assessment of their association with asthma incidence identified 9 CpGs in males and 6 CpGs in females. DNAm at 4 of these 15 CpGs showed statistically significant mediation effects (p-value < 0.05). At two of the 4 CpGs (cg23632109 and cg10817500), DNAm completely mediated the association (i.e., only statistically significant indirect effects were identified). In the ALSPAC cohort, at all four CpGs, the same direction of mediating effects were observed as those found in the IoW cohort, although statistically insignificant.

Conclusion: The association of BMI trajectory in childhood with asthma incidence at young adulthood is possibly mediated by DNAm.
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http://dx.doi.org/10.1186/s13223-021-00575-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299682PMC
July 2021

Phase-Selective Synthesis of Ultrathin FeTe Nanoplates by Controllable Fe/Te Atom Ratio in the Growth Atmosphere.

Small 2021 Aug 16;17(33):e2101616. Epub 2021 Jul 16.

Hunan Key Laboratory of Two-Dimensional Materials, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, China.

Phase controllable synthesis of 2D materials is of significance for tuning related electrical, optical, and magnetic properties. Herein, the phase-controllable synthesis of tetragonal and hexagonal FeTe nanoplates has been realized by a rational control of the Fe/Te ratio in a chemical vapor deposition system. Using density functional theory calculations, it has been revealed that with the change of the Fe/Te ratio, the formation energy of active clusters changes, causing the phase-controllable synthesis of FeTe nanoplates. The thickness of the obtained FeTe nanoplates can be tuned down to the 2D limit (2.8 nm for tetragonal and 1.4 nm for hexagonal FeTe). X-ray diffraction pattern, transmission electron microscopy, and high resolution scanning transmission electron microscope analyses exhibit the high crystallinity of the as-grown FeTe nanoplates. The two kinds of FeTe nanoflakes show metallic behavior and good electrical conductivity, featuring 8.44 × 10 S m for 9.8 nm-thick tetragonal FeTe and 5.45 × 10 S m for 7.6 nm-thick hexagonal FeTe. The study provides an efficient and convenient route for tailoring the phases of FeTe nanoplates, which benefits to study phase-sensitive properties, and may pave the way for the synthesis of other multiphase 2D nanosheets with controllable phases.
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http://dx.doi.org/10.1002/smll.202101616DOI Listing
August 2021

Artificial intelligence in digital cariology: a new tool for the diagnosis of deep caries and pulpitis using convolutional neural networks.

Ann Transl Med 2021 May;9(9):763

Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, the Affiliated Hospital of Stomatology of Chongqing Medical University, Chongqing, China.

Background: An accurate diagnosis of deep caries and pulpitis on periapical radiographs is a clinical challenge.

Methods: A total of 844 radiographs were included in this study. Of the 844, 717 (85%) were used for training and 127 (15%) were used for testing the three convolutional neural networks (CNNs) (VGG19, Inception V3, and ResNet18). The performance [accuracy, precision, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC)] of the CNNs were evaluated and compared. The CNN model with the best performance was further integrated with clinical parameters to see whether multi-modal CNN could provide an enhanced performance. The Gradient-weighted Class Activation Mapping (Grad-CAM) technique illustrates what image feature was the most important for the CNNs.

Results: The CNN of ResNet18 demonstrated the best performance [accuracy =0.82, 95% confidence interval (CI): 0.80-0.84; precision =0.81, 95% CI: 0.73-0.89; sensitivity =0.85, 95% CI: 0.79-0.91; specificity =0.82, 95% CI: 0.76-0.88; and AUC =0.89, 95% CI: 0.86-0.92], compared with VGG19 and Inception V3 as well as the comparator dentists. Therefore, ResNet18 was chosen to integrate with clinical parameters to produce the multi-modal CNN of ResNet18 + C, which showed a significantly enhanced performance (accuracy =0.86, 95% CI: 0.84-0.88; precision =0.85, 95% CI: 0.76-0.94; sensitivity =0.89, 95% CI: 0.83-0.95; specificity =0.86, 95% CI: 0.79-0.93; and AUC =0.94, 95% CI: 0.91-0.97).

Conclusions: The CNN of ResNet18 showed good performance (accuracy, precision, sensitivity, specificity, and AUC) for the diagnosis of deep caries and pulpitis. The multi-modal CNN of ResNet18 + C (ResNet18 integrated with clinical parameters) demonstrated a significantly enhanced performance, with promising potential for the diagnosis of deep caries and pulpitis.
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http://dx.doi.org/10.21037/atm-21-119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246233PMC
May 2021

Reply to: "Questions remain about the biolability of dissolved black carbon along the combustion continuum".

Nat Commun 2021 07 13;12(1):4282. Epub 2021 Jul 13.

Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education/ Center for Frontier Science of Deep Ocean and Earth System, Ocean University of China, Qingdao, China.

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http://dx.doi.org/10.1038/s41467-021-24478-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277776PMC
July 2021

The inhibition of GHR enhanced cytotoxic effects of etoposide on neuroblastoma.

Cell Signal 2021 Oct 9;86:110081. Epub 2021 Jul 9.

Department of Pediatrics, Yancheng Third People's Hospital, Southeast University, Yancheng 224000, China. Electronic address:

Etoposide, a DNA damage-inducing agent, is widely used to treat neuroblastoma. Etoposide binds to and inhibits topoisomerase II, thereby inducing the DNA damage response. However, the underlying mechanism of etoposide resistance in neuroblastoma remains unclear. The results of the present study revealed that etoposide upregulated growth hormone receptor (GHR) expression levels in etoposide-resistant neuroblastoma cells, suggesting that GHR upregulation may be involved in the underlying mechanism of etoposide resistance. Thus, the combined effect of GHR knockdown and etoposide treatment on cell viability, apoptosis and migration in vitro, as well as tumor growth in mouse xenograft models in vivo, was subsequently analyzed. The results of cell viability and colony formation assays demonstrated that GHR knockdown enhanced the inhibitory effects of etoposide on cell viability and sensitized cells to etoposide. The enhanced cell viability was discovered to be, at least in part, due to the increase in etoposide-induced apoptosis following GHR knockdown. Moreover, the knockdown of GHR enhanced the inhibitory effect of etoposide on cell migration. Mouse xenograft studies confirmed the effects of GHR silencing in etoposide-resistant neuroblastoma progression in vivo. Furthermore, the effects of GHR knockdown in etoposide resistance were hypothesized to occur via the inactivation of the MEK/ERK signaling pathway. In conclusion, the results of the present study provided novel insight into the underlying mechanism of etoposide resistance and a potential target for the treatment of etoposide-resistant neuroblastoma.
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http://dx.doi.org/10.1016/j.cellsig.2021.110081DOI Listing
October 2021

Ferroptosis as a new therapeutic opportunity for nonviral liver disease.

Eur J Pharmacol 2021 Oct 9;908:174319. Epub 2021 Jul 9.

Institute of Basic and Translational Medicine, Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, Shaanxi, 710021, China. Electronic address:

Nonviral liver disease is a global public health problem due to its high mortality and morbidity. However, its underlying mechanism is unclear. Ferroptosis is a novel form of cell death that is involved in a variety of disease processes. Both abnormal iron metabolism (e.g., iron overload) and lipid peroxidation, which is induced by deletion of glutathione (GSH) or glutathione peroxidase 4 (GPX4), and the accumulation of polyunsaturated fatty acid-containing phospholipids (PUFA-PLs) trigger ferroptosis. Recently, ferroptosis has been involved in the pathological process of nonviral liver diseases [including alcohol-related liver disease (ALD); nonalcoholic fatty liver disease (NAFLD); hereditary hemochromatosis (HH); drug-, ischemia/reperfusion- or immune-induced liver injury; liver fibrosis; and liver cancer]. Hepatocyte ferroptosis is activated in ALD; NAFLD; HH; drug-, ischemia/reperfusion- or immune-induced liver injury; and liver fibrosis, whereas hepatic stellate cell and liver cancer cell ferroptosis are inhibited in liver fibrosis and liver cancer, respectively. Thus, ferroptosis is an ideal target for nonviral liver diseases. In the present review, we discuss the latest findings on ferroptosis and potential drugs targeting ferroptosis for nonviral liver diseases. This review will highlight further directions for the treatment and prevention of nonviral liver diseases.
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http://dx.doi.org/10.1016/j.ejphar.2021.174319DOI Listing
October 2021

Childhood food allergy and food allergen sensitisation are associated with adult airways disease: A birth cohort study.

Pediatr Allergy Immunol 2021 Jul 9. Epub 2021 Jul 9.

David Hide Asthma and Allergy Research Centre, Isle of Wight, UK.

Background: Childhood food allergy (FA) and food allergen sensitization (FAS) are associated with allergic airway disease(s) [AAD] (asthma and rhinitis) in childhood. However, the associations between childhood FA/FAS and AAD in adulthood are not well described.

Methods: We investigated the longitudinal relationship between childhood FA/FAS to common food allergens and AAD at 18 and 26 years, in the Isle of Wight birth cohort. Study subjects (N = 1456) were followed up at fixed time points from ages 1-26 years for FA/FAS status. AAD were evaluated from 4 years onwards. The associations between FA/FAS and AAD were assessed with univariate analyses and then multivariable logistic regression, adjusting for clinically relevant co-variates.

Results: Food allergy at 4 years was significantly associated with asthma at 18 years [adjusted odds ratio (aOR): 2.75, 95% CI: 1.53-4.92, p = .001] and 26 years (aOR: 2.62, 95% CI: 1.32-5.20, p = .006). Conversely, childhood FA was not associated with adulthood rhinitis whatsoever. While FAS at ages 4 and 10 were associated with both AAD, the associations between FAS and rhinitis were less robust relative to asthma.

Conclusion: Childhood FA increased the odds of asthma during adulthood by nearly threefold. Additionally, childhood FAS was also associated with increased odds of asthma in adulthood. Conversely, FAS but not FA in childhood was associated with rhinitis in adulthood. We suggest that children with FA/FAS should be followed up to facilitate early detection and intervention of subsequent AAD, particularly asthma.
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http://dx.doi.org/10.1111/pai.13592DOI Listing
July 2021

Identification of key genes involved in the recurrence of glioblastoma multiforme using weighted gene co-expression network analysis and differential expression analysis.

Bioengineered 2021 Dec;12(1):3188-3200

Department of Physiology of Basic medicine college, Guizhou Medical University, Weifang, Shandong, China.

Glioblastoma multiforme (GBM) is the most fatal malignancy, and despite extensive treatment, tumors inevitably recur. This study aimed to identify recurrence-associated molecules in GBM. The gene expression profile GSE139533, containing 70 primary and 47 recurrent GBM tissues and their corresponding clinical traits, was downloaded from the Gene Expression Omnibus (GEO) database and used for weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis. After identifying the hub genes which differentially expressed in recurrent GBM tissues and in the gene modules correlated with recurrence, data from the Chinese Glioma Genome Atlas (CCGA) and The Cancer Genome Atlas (TCGA) databases were analyzed with GSE43378 to determine the relationship between hub genes and patient prognosis. The diagnostic value of the identified hub genes was verified using 52 GBM tissues. Three gene modules were correlated with recurrence and 2623 genes were clustered in these clinically significant modules. Among these, 13 genes - and - were differentially expressed in recurrent GBM samples; low and expression predicted poor outcomes. and expression showed weak positive relationships with Karnofsky performance scale scores. Additionally, and expression was found to be decreased in our recurrent GBM samples compared with that in primary samples; these genes exhibited high diagnostic value in distinguishing recurrent samples from primary samples. Our findings indicate that and might be involved in GBM recurrence and act as potential biomarkers for this condition.
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http://dx.doi.org/10.1080/21655979.2021.1943986DOI Listing
December 2021

Sex-specific longitudinal association of DNA methylation with lung function.

ERJ Open Res 2021 Jul 5;7(3). Epub 2021 Jul 5.

NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton, UK.

Investigating whether DNA methylation (DNA-M) at an earlier age is associated with lung function at a later age and whether this relationship differs by sex could enable prediction of future lung function deficit. A training/testing-based technique was used to screen 402 714 cytosine-phosphate-guanine dinucleotide sites (CpGs) to assess the longitudinal association of blood-based DNA-M at ages 10 and 18 years with lung function at 18 and 26 years, respectively, in the Isle of Wight birth cohort (IOWBC). Multivariable linear mixed models were applied to the CpGs that passed screening. To detect differentially methylated regions (DMRs), DMR enrichment analysis was conducted. Findings were further examined in the Avon Longitudinal Study of Parents and Children (ALSPAC). Biological relevance of the identified CpGs was assessed using gene expression data. DNA-M at eight CpGs (five CpGs with forced expiratory volume in 1 s (FEV) and three CpGs with FEV/forced vital capacity (FVC)) at an earlier age was associated with lung function at a later age regardless of sex, while at 13 CpGs (five CpGs with FVC, three with FEV and five with FEV/FVC), the associations were sex-specific (p <0.05) in IOWBC, with consistent directions of association in ALSPAC (IOWBC-ALSPAC consistent CpGs). cg16582803 () and cg14083603 () were replicated in ALSPAC for main and sex-specific effects, respectively. Among IOWBC-ALSPAC consistent CpGs, DNA-M at cg01376079 () and cg07557690 () was associated with gene expression both longitudinally and cross-sectionally. In total, 57 and 170 DMRs were linked to lung function longitudinally in males and females, respectively. CpGs showing longitudinal associations with lung function have the potential to serve as candidate markers in future studies on lung function deficit prediction.
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http://dx.doi.org/10.1183/23120541.00127-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255542PMC
July 2021

Fat mass assessment using the triceps skinfold thickness enhances the prognostic value of the Global Leadership Initiative on Malnutrition criteria in patients with lung cancer.

Br J Nutr 2021 Jul 5:1-11. Epub 2021 Jul 5.

Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing400042, People's Republic of China.

The present study evaluated whether fat mass assessment using the triceps skinfold (TSF) thickness provides additional prognostic value to the Global Leadership Initiative on Malnutrition (GLIM) framework in patients with lung cancer (LC). We performed an observational cohort study including 2672 LC patients in China. Comprehensive demographic, disease and nutritional characteristics were collected. Malnutrition was retrospectively defined using the GLIM criteria, and optimal stratification was used to determine the best thresholds for the TSF. The associations of malnutrition and TSF categories with survival were estimated independently and jointly by calculating multivariable-adjusted hazard ratios (HR). Malnutrition was identified in 808 (30·2 %) patients, and the best TSF thresholds were 9·5 mm in men and 12 mm in women. Accordingly, 496 (18·6 %) patients were identified as having a low TSF. Patients with concurrent malnutrition and a low TSF had a 54 % (HR = 1·54, 95 % CI = 1·25, 1·88) greater death hazard compared with well-nourished individuals, which was also greater compared with malnourished patients with a normal TSF (HR = 1·23, 95 % CI = 1·06, 1·43) or malnourished patients without TSF assessment (HR = 1·31, 95 % CI = 1·14, 1·50). These associations were concentrated among those patients with adequate muscle mass (as indicated by the calf circumference). Additional fat mass assessment using the TSF enhances the prognostic value of the GLIM criteria. Using the population-derived thresholds for the TSF may provide significant prognostic value when used in combination with the GLIM criteria to guide strategies to optimise the long-term outcomes in patients with LC.
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http://dx.doi.org/10.1017/S0007114521002531DOI Listing
July 2021

[Expression of CD44 in Tumor Tissue and Serum of Small Cell Lung Cancer and Its Clinical Prognostic Significance].

Zhongguo Fei Ai Za Zhi 2021 Aug 30;24(8):583-590. Epub 2021 Jun 30.

Department of Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, 
Capital Medical University, Beijing 101149, China.

Background: Small cell lung cancer (SCLC) is a highly aggressive malignancy characterized by rapid growth, early metastasis and acquired therapeutic resistance, and the prognosis is extremely poor. Studies have proved that the stem cell marker CD44 is correlated with tumor recurrence and treatment resistance, however, there are limited reports yet concerning on the CD44 expression and its clinical prognostic significance in SCLC patients. The purpose of this study is to investigate the expression of CD44 in tumor tissues as well as serum of SCLC patients and explore its correlation with the clinical characteristics, therapeutic effect and prognosis.

Methods: The tumor tissues and serum samples of 47 newly diagnosed SCLC patients were collected. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to detect CD44. The relationship between CD44 level and the clinical characteristics as well as prognosis of the patients was analyzed.

Results: The stem cell marker CD44 was detectable both in serum sample and tumor tissue of SCLC patients. The positive rate of CD44 in tumor tissue was significantly higher in patients with performance status (PS) 2 than that of patients with PS 0-1 (85.71% vs 30%, P=0.017). Patients were divided in to different groups according to the treatment efficacy. The CD44 immunohistochemical score and serum level in the disease progression group were significantly higher than those in the disease control group, and the differences were statistically significant (P=0.006, P=0.034), Univariate analysis depicted that the progression-free survival (PFS) of CD44 positive patients was significantly shorter than that of CD44 negative patients (5.23 mon vs 9.03 mon, P=0.036).

Conclusions: The positive expression of CD44 in tumor tissues of pre-treatment SCLC patients is correlated with poor PFS. The clinical significance of CD44 is worthy to be further studied.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.104.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387646PMC
August 2021

miR-509-5p anti-infection response for mycoplasma pneumonia in sheep by targeting NF-κB pathway.

Vet Immunol Immunopathol 2021 Aug 5;238:110275. Epub 2021 Jun 5.

College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang, China. Electronic address:

MicroRNAs play a key role in Mannan-binding lectin-mediated resistance to Mycoplasma ovipneumoniae pneumonia, by regulating the translation of mRNAs of target genes, thereby regulating the immune response. Additionally, TRAF6 is a key molecule in Toll-like receptor signal transduction, which mediates inflammation and apoptosis signaling pathways and is widely involved in inflammation and immune response. While the molecular regulation mechanism has not been reported. In this study, we screened differentially expressed miRNAs and genes of Anti-infection for M. pneumonia on Sheep, through relevant bioinformatics analysis. Further, the effect of differential expression of NF-κB signaling pathway related genes on the molecular mechanism of M. pneumonia was detected. We used miRNA-mRNA integrated analysed, the target gene TRAF6 of miR-509-5p was selected. TRAF6 dual luciferase reporter vector was co-transfected into HEK 293T cells and primary sheep respiratory mucosal epithelial cells to detect changes in luciferase activity. qRT-PCR was used to analyze the effect of miR-509-5p on the expression and regulation of TRAF6 and other genes related to the NF-κB signaling pathway. The result confirmed that TRAF6 was a target gene of miR-509-5p. Compared with miR-509-5p-NC group, the luciferase activity of miR-509-5p group was significantly down-regulated (P < 0.01). Further, in sheep respiratory mucosal epithelial cells, miR-509-5p mimic could significantly down-regulate the fold change value of TRAF6 (P < 0.01). On the contrary, miR-509-5p-inhibitor up-regulated the fold change value of TRAF6 (P < 0.05). Interestingly, the expression levels of other genes were different. Among them, miR-509-5p mimic significantly up-regulated TLR4 and IRAK4 (P < 0.05), significantly down-regulated TAK1 (P < 0.05) and NF-κB (P < 0.01). miR-509-5p-inhibitor significantly up-regulated NF-κB (P < 0.05) and TAK1 (P < 0.01). miR-509-5p targets TRAF6 to affect the expression of downstream genes, which negatively regulates the NF-κB pathway, thereby affecting the inflammatory response.
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http://dx.doi.org/10.1016/j.vetimm.2021.110275DOI Listing
August 2021
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